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Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.PloS One 2015Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies looking at acquired drug resistance (ADR) are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.
METHODS
Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1) HIV and 2) baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.
RESULTS
Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%). Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11); there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%). Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST) was 0.1% (5th to 95th percentile 0.07 to 3.2%).
CONCLUSION
Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely to contribute to the outcome of ADR. The multifactorial aetiology of ADR in a programmatic setting should be further evaluated via appropriately designed studies.
Topics: AIDS-Related Opportunistic Infections; Antitubercular Agents; Drug Resistance, Bacterial; Humans; Isoniazid; Rifamycins; Risk; Tuberculosis
PubMed: 26406228
DOI: 10.1371/journal.pone.0139017 -
Iranian Journal of Public Health Feb 2023The present systematic review aimed to investigate the drug susceptibility patterns of Iranian clinical isolates to antifungal drugs (azoles, polyenes, and... (Review)
Review
BACKGROUND
The present systematic review aimed to investigate the drug susceptibility patterns of Iranian clinical isolates to antifungal drugs (azoles, polyenes, and echinocandins).
METHODS
Six electronic databases including "PubMed," "Scopus," "Web of Science," "IranDoc", "SID", and "Magiran" were searched from May 2000 to June 2021. The susceptibility of 6322 strains from 19967 patients against 14 antifungal drugs was evaluated according to CLSI method.
RESULTS
The pooled prevalence of antifungal resistance ranged from 0% to 26%. The lowest resistance levels among azoles were observed in luliconazole with a frequency of 0% and voriconazole of 3.94%.
CONCLUSION
Due to the emergence of multi-drug resistant rational drug prescription based on the anti-fungal stewardship strategy and therapeutic drug monitoring is warranted.
PubMed: 37089147
DOI: 10.18502/ijph.v52i2.11874 -
Antibiotics (Basel, Switzerland) Aug 2019Antibiotic resistance (ABR) is one of the biggest threats to global health, especially in China. This study aims to analyze the published literature on the clinical and... (Review)
Review
Antibiotic resistance (ABR) is one of the biggest threats to global health, especially in China. This study aims to analyze the published literature on the clinical and economic impact of ABR or multi-drug resistant (MDR) bacteria compared to susceptible bacteria or non-infection, in mainland China. English and Chinese databases were searched to identify relevant studies evaluating mortality, hospital stay, and hospital costs of ABR. A meta-analysis of mortality was performed using a random effects model. The costs were converted into 2015 United States (US) dollars. Of 13,693 studies identified, 44 eligible studies were included. Twenty-nine investigated the impact of ABR on hospital mortality, 37 were focused on hospital stay, and 21 on hospital costs. Patients with ABR were associated with a greater risk of overall mortality compared to those with susceptibility or those without infection (odds ratio: 2.67 and 3.29, 95% confidence interval: 2.18-3.26 and 1.71-6.33, < 0.001 and < 0.001, respectively). The extra mean total hospital stay and total hospital cost were reported, ranging from 3 to 46 days, and from US$238 to US$16,496, respectively. Our study indicates that ABR is associated with significantly higher mortality. Moreover, ABR is not always, but usually, associated with significantly longer hospital stay and higher hospital costs.
PubMed: 31405146
DOI: 10.3390/antibiotics8030115 -
Current Medicinal Chemistry 2018Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a...
BACKGROUND
Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients.
OBJECTIVE
The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD.
METHOD
We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS).
RESULTS
We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies).
CONCLUSION
Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 29278206
DOI: 10.2174/0929867325666171222163645 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Antiviral Therapy 2013The increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance.... (Review)
Review
BACKGROUND
The increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summarizes the available information on drug resistance in adults in resource-limited settings.
METHODS
The online databases PubMed and Google Scholar, pertinent conference abstracts and references from relevant articles were searched for publications available before November 2011. Data collected after ART rollout were reviewed.
RESULTS
A total of 7 studies fulfilled the criteria for the analysis of acquired drug resistance and 22 fulfilled the criteria for the analysis of transmitted drug resistance (TDR). Acquired resistance was detected in 7.2% of patients on ART for 6-11 months, 11.1% at 12-23 months, 15.0% at 24-35 months, and 20.7% at ≥ 36 months. Multi-class drug resistance increased steadily with time on ART. The overall rate of TDR in all resource-limited countries studied was 6.6% (469/7,063). Patients in countries in which ART had been available for ≥ 5 years were 1.7 × more likely to have TDR than those living in a country where ART had been available for <5 years (P<0.001). The reported prevalence of TDR was 5.7% (233/4,069) in Africa, 7.6% (160/2,094) in Asia and 8.4% (76/900) in Brazil.
CONCLUSIONS
The emergence of drug resistance following access to ART in resource-limited settings resembles what was seen in resource-rich countries and highlights the need for virological monitoring for drug failure, drug resistance testing and alternative drug regimens that have proven beneficial in these resource-rich settings.
Topics: Adult; Anti-HIV Agents; Developing Countries; Drug Resistance, Viral; HIV Infections; HIV-1; Humans; Prevalence
PubMed: 23052978
DOI: 10.3851/IMP2437 -
Clinical Microbiology and Infection :... Jun 2021People living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
People living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR).
METHODS
We searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance.
RESULTS
In total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcusaureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36-3.30) higher odds for colonization and 1.90 (95%CI 1.45-2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75-2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae.
CONCLUSION
This review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; HIV Infections; HIV-1; Humans
PubMed: 33813126
DOI: 10.1016/j.cmi.2021.03.026 -
PloS One 2016In recent years, drug resistant tuberculosis (DR-TB) particularly the emergence of multi-drug-resistant tuberculosis (MDR-TB) has become a major public health issue. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, drug resistant tuberculosis (DR-TB) particularly the emergence of multi-drug-resistant tuberculosis (MDR-TB) has become a major public health issue. The most recent study regarding the prevalence of drug-resistant tuberculosis in mainland China was a meta-analysis published in 2011, and the subjects from the included studies were mostly enrolled before 2008, thus making it now obsolete. Current data on the national prevalence of DR-TB is needed. This review aims to provide a comprehensive and up-to-date assessment of the status of DR-TB epidemic in mainland China.
METHODS
A systematic review and meta-analysis of studies regarding the prevalence of drug-resistant tuberculosis in mainland China was performed. Pubmed/MEDLINE, EMBASE, the Cochrane central database, the Chinese Biomedical Literature Database and the China National Knowledge Infrastructure Database were searched for studies relevant to drug-resistant tuberculosis that were published between January 1, 2012 and May 18, 2015. Comprehensive Meta-Analysis (V2.2, Biostat) software was used to analyse the data.
RESULTS
A total of fifty-nine articles, published from 2012 to 2015, were included in our review. The result of this meta-analysis demonstrated that among new cases, the rate of resistance to any drug was 20.1% (18.0%-22.3%; n/N = 7203/34314) and among retreatment cases, the rate was 49.8% (46.0%-53.6%; n/N = 4155/8291). Multi-drug resistance among new and retreatment cases was 4.8% (4.0%-5.7%; n/N = 2300/42946) and 26.3% (23.1%-29.7%; n/N = 3125/11589) respectively. The results were significantly heterogeneous (p<0.001, I2 tests). Resistance to isoniazid was the most common resistance observed, and HRSE (H: isoniazid; R: rifampicin; S: streptomycin; E: ethambutol) was the most common form for MDR among both new and retreatment cases. Different drug resistance patterns were found by subgroup analysis according to geographic areas, subject enrolment time, and methods of drug susceptibility test (DST).
CONCLUSIONS
The prevalence of resistance to any drug evidently dropped for both new and retreatment cases, and multi-drug resistance declined among new cases but became more prevalent among retreatment cases compared to the data before 2008. Therefore, drug-resistant tuberculosis, particularly multi-drug-resistant tuberculosis among retreatment TB cases is a public health issue in China that requires a constant attention in order to prevent increase in MDR-TB cases.
Topics: China; Humans; Prevalence; Tuberculosis, Multidrug-Resistant
PubMed: 26859846
DOI: 10.1371/journal.pone.0148041 -
The Indian Journal of Tuberculosis Jan 2024Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted... (Meta-Analysis)
Meta-Analysis Review
Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.
Topics: Adult; Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Diarylquinolines; Treatment Outcome; Nitroimidazoles; Oxazoles
PubMed: 38296395
DOI: 10.1016/j.ijtb.2023.05.005 -
Clinical Infectious Diseases : An... Nov 2013Prospective time-trend analyses on shifting etiology and trends of drug resistance in enteric fever are scarce. Using published and unpublished datasets from Nepal, we... (Meta-Analysis)
Meta-Analysis Review
Prospective time-trend analyses on shifting etiology and trends of drug resistance in enteric fever are scarce. Using published and unpublished datasets from Nepal, we performed a systematic review and meta-analysis to understand the trends in etiology and resistance to antimicrobials that have occurred since 1993. Thirty-two studies involving 21 067 Salmonella enterica serotype Typhi (ST) and S. enterica serotype Paratyphi A (SPA) isolates were included. There was an increasing trend in enteric fever caused by SPA during the last 2 decades (P < .01). We observed sharply increasing trends in resistance to nalidixic acid and ciprofloxacin for both ST and SPA. In contrast, multi-drug resistance (MDR), resistance to traditional first-line antibiotics such as chloramphenicol and co-trimoxazole have significantly decreased for both organisms. The resistance to ceftriaxone has remained low, suggesting it is likely to remain useful as a reserve antibiotic for treatment. Trends in decreasing resistance to traditional first-line antibiotics and decreasing MDR provide an opportunity to reconsider these first-line antimicrobials as therapeutic options.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Nepal; Salmonella Infections; Salmonella enterica
PubMed: 23985342
DOI: 10.1093/cid/cit563